Tissue-specific differences, singularities and changes in intercellular adhesiveness are widely invoked to explain the preferential associations or "affinities" of cells; their grouping into tissues; the spreading or migratory properties of these tissues and their organization into anatomically "correct" structures: and, at least in part, the tissue disorganization and cell dispersion that occurs in malignancy. Cellular adhesive disorders may also underlie certain morphogenetic errors that result in specific birth defects. Understanding these fundamental phenomena requires an understanding of the regulation, chemistry and physics of intercellular adhesion. The proposed experiments are directed toward that goal. Using monoclonal antibodies directed against two specific adhesion systems we have identified on the surfaces of embryonic retinal and certain other cells, we propose to ask the following questions. What other tissues share each of these recognition system? Is each a single system or a family of related systems? What is the role, if any, of each of these systems in the "mapping" of the retina onto the optic tectum, which shares them? Is either system localized to a particular kind of intercellular junction or attachment region? Is it a constituent of that type of junction in other tissues? What are the molecules (glycoproteins? Molecular weights?) that constitute each adhesion system? Are there distinct lock and key components or are they "homophilic"? What is the contribution of each system to the total cohesive intensity (alpha) and spreading potential of a series of cell populations displaying it? These experiments will utilize already-developed techniques of spectrophotometry, immunology, fluorescence microscopy, immunoelectron microscopy affinity chromatography, gel electrophoresis, an automatic-recording cell "aggregometer" for intercellular adhesive rate comparisons, and a continuous-recording tissue surface tensiometer for intercellular adhesive intensity measurements.